Jacobsson L, Lundholm L, Wingren G
Acta Pharmacol Toxicol (Copenh). 1984 Sep;55(3):174-82. doi: 10.1111/j.1600-0773.1984.tb02033.x.
Advanced coronary atherosclerosis was produced in 30 mini-pigs by a combination of a hypercholesterolaemic diet and X-irradiation to the precordial region. Within 11-25 weeks after the irradiation, 13 of the 30 animals died a sudden death probably caused by coronary atherosclerosis. The contents of free and ester-bound cholesterol in the right coronary artery were significantly higher in the animals which died spontaneously than in surviving animals. In an untreated group of 12 animals 7 died whereas in a group treated with beta-pyridylcarbinol only 1 out of 5 died. In the coronary arteries, the contents of both free and ester-bound cholesterol were significantly lower in the beta-pyridylcarbinol-treated animals. In a sulfinpyrazone-treated group 3 out of 8, and in a metoprolol-treated group 2 out of 5 animals died. None of these drugs reduced the accumulation of cholesterol in the coronary arteries. The rate of sudden death was 26 +/- 6% (P less than 0.05) lower in the combined group of treated animals than in the untreated ones. By regular ECG recordings, signs which could predict the fatal outcome of the experiment were looked for. Although depressed ST segments were present before death in a few animals, this was not a regular phenomenon. It is concluded that advanced coronary atherosclerosis in mini-pigs often leads to sudden death and that this animal model seems suitable for testing the potential therapeutic effects of drugs.
通过高胆固醇饮食和对心前区进行X射线照射相结合的方法,在30只小型猪身上诱发了严重的冠状动脉粥样硬化。在照射后的11至25周内,30只动物中有13只因冠状动脉粥样硬化突然死亡。自然死亡动物右冠状动脉中游离胆固醇和酯化胆固醇的含量显著高于存活动物。在未经治疗的12只动物组中,7只死亡;而在仅用β-吡啶甲醇治疗的组中,5只中有1只死亡。在冠状动脉中,用β-吡啶甲醇治疗的动物,游离胆固醇和酯化胆固醇的含量均显著降低。在使用磺吡酮治疗的组中,8只中有3只死亡;在使用美托洛尔治疗的组中,5只中有2只死亡。这些药物均未减少冠状动脉中胆固醇的积累。治疗动物的联合组猝死率比未治疗组低26±6%(P<0.05)。通过定期进行心电图记录,寻找能够预测实验致命结果的迹象。尽管少数动物在死亡前出现ST段压低,但这并非常见现象。得出的结论是,小型猪的严重冠状动脉粥样硬化常导致猝死,且该动物模型似乎适合用于测试药物的潜在治疗效果。